Kurt A. Wargo

Comparison of the Modification of Diet in Renal Disease and Cockcroft-Gault Equations for Antimicrobial Dosage Adjustments

Background: Direct measurement of glomerular filtration rate (GFR) is considered to be the most accurate method of assessing kidney function, albeit difficult and costly. With the derivation of the Modification of Diet in Renal Disease (MDRD) equation to estimate GFR in patients with chronic kidney disease, questions exist as to whether this method should be preferred over the Cockcroft–Gault (CG) equation when making dosage adjustments for renally eliminated antimicrobials. Objective: To determine whether a difference exists when making antimicrobial dosage adjustments in patients with chronic kidney disease based on estimation of GFR using the MDRD and CG equations. Methods: We conducted an observational analysis of 409 patients with chronic kidney disease who were admitted to a tertiary care facility with an inpatient dialysis center and nephrology unit. GFR was calculated using both the 4- or 6-variable MDRD equation and the CG equation and compared using correlation and Bland–Altman methodology. Dosage discordance rates of the selected antimicrobials were determined on the basis of manufacturer renal dose recommendations. Results: Average ± SD GFR for all patients using the CG equation was 34.8 ± 12 mL/min and, using the MDRD equation, was 40.2 ± 12 mL/min (absolute mean difference 5.40; 95% CI 4.66 to 6.15; p < 0.001). The correlation coefficient between the 2 estimations, among all patients, was excellent (r=0.80). The Bland–Altman plot yielded limits of agreement of -9.8 and 20.6; thus, the MDRD estimation may range from 9.8 mL/min below to 20.6 mL/min above the CG estimation for 95% of the cases. A discordance rate of 21–37% (p < 0.001) existed among the recommended dosing adjustments of the selected antimicrobials. Conclusions: This analysis demonstrated statistically significant differences between the CG and MDRD equations, resulting in different dosing recommendations in 21–37% of patients. The clinical significance of these differences is uncertain in the absence of data regarding clinical outcomes that would result from the use of the discordant doses.

Aminoglycoside-Induced Nephrotoxicity

Aminoglycosides are among the oldest antibiotics available to treat serious infections caused by primarily, Gram-negative bacteria. The most commonly utilized parenteral agents in this class include gentamicin, tobramycin and amikacin. Aminoglycosides are concentration-dependent, bactericidal agents that undergo active transport into the cell where they inhibit protein synthesis on the 30S subunit of the bacterial ribosome. As the use of aminoglycosides became more widespread, the toxic effects of these agents, most notably ototoxicity and nephrotoxicity, became more apparent. When other, safer, antimicrobial agents became available, the use of aminoglycosides sharply declined. The development of multi-drug resistance among bacteria has now lead clinicians to reexamine the role of the aminoglycosides in the treatment of serious infections. This review will revisit the mechanism and risk factors for the development of aminoglycoside-induced nephrotoxicity, as well as strategies to prevent patients from developing nephrotoxicity.

Evaluation of the Chronic Kidney Disease Epidemiology Collaboration Equation for Dosing Antimicrobials

Background: Since the derivation of the Modification of Diet in Renal Disease (MORD) equation for estimating glomerular filtration rate (GFR), investigators determined that it cannot be used for drug dosing. In 2009, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) derived an equation that was more accurate than the MORD estimation of GFR. Therefore, questions exist about which method should be preferred in making dosage adjustments for renally eliminated antimicrobials. Objective: To determine whether a difference exists when making antimicrobial dosage adjustments in patients with CKD based on estimation of GFR using the CKD-EPI and Cockcroft-Gault equations. Methods: A database of 409 patients with CKD admitted to a tertiary care facility was used. GFR was calculated using both the CKD-EPI equation(s) and the Cockcroft-Gault equation and compared using correlation and Bland-Altman methodology. Dosage discordance rates of antimicrobials were determined. Results: Average GFRs for all patients using the Cockcroft-Gault and CKD-EPI equations were 34.8 ± 12 mL/rnin and 39.9 ± 13 mL/min, respectively (5.09 [95% CI 4.60 to 5.59]; p < 0.001). The correlation coefficient between the 2 estimations was high (r = 0.91). The Bland-Altman plot yielded limits of agreement of 15.3 and -5.1; thus, the CKD-EPI estimation may range from 5.1 mL/min below to 15.3 mL/min above the Cockcroft-Gault estimation for 95% of the cases. A discordance rate of 15–25% existed among the recommended dosing adjustments of the selected antimicrobials when comparing the Ccckcroft-Gault and CKD-EPI estimations. Conclusions: Though this study did not determine which equation should be selected to dose adjust antimicrobials, it demonstrated statistically significant differences between the Cockcroft-Gault and CKD-EPI equations. The clinical significance of these differences is uncertain in the absence of data assessing clinical outcomes that result from the use of the discordant doses. Clinical judgment should be employed when making renal dosage adjustments of antimicrobials.

A possible case of saw palmetto-induced pancreatitis.

A 65-year-old male with a history of diabetes, hypertension, hyperlipidemia, gout, Barrett esophagitis, and chronic gastritis developed acute pancreatitis after taking one week of the herbal medicine, saw palmetto, for symptoms related to benign prostatic hyperplasia (BPH). Ultrasound and computed tomography ruled out cholelithiasis and obstruction, triglycerides were normal, and he had no recent infection or trauma. He had a history of occasional alcohol consumption, though there was no recent increased intake. The most likely cause of pancreatitis in this case was saw palmetto. Saw palmetto (Serenoa repens) is an herbal medication used primarily in the treatment of symptoms related to BPH. It has a high content of fatty acids and phytosterols which are thought to exert their effects by inhibiting the enzyme 5-alpha-reductase, thereby preventing the conversion of testosterone into dihydrotestosterone (DHT). It has been postulated that saw palmetto directly stimulates estrogenic receptors and inhibits progesterone receptors in the prostate tissue. A previous report implicated the estrogen/antiandrogen properties of saw palmetto as inducing hepatotoxicity in a patient. Additionally, it has also been postulated that stimulation of the estrogenic receptors may lead to increased triglyceride levels or induction of a hypercoagulable state that leads to pancreatic necrosis. Finally, inhibition of cyclooxygenase, a property of saw palmetto, may be linked to acute pancreatitis. Acute pancreatitis, a serious and sometimes fatal disorder may occur secondary to medications. Although the mechanism is not fully known, this is the second case of acute pancreatitis that has been documented secondary to the herbal medication saw palmetto. It is important for clinicians to obtain detailed medication histories, including over-the-counter and herbal medications, in order to prevent further complications from occurring.

Alternate-Day Statin Therapy for the Treatment of Hyperlipidemia

Objective: To evaluate the safety, efficacy, and cost of alternate-day statin therapy in the treatment of hyperlipidemia. Data Sources: Systematic searches were conducted for primary literature sources involving alternative statin regimens using PubMed, EMBASE, Google Scholar, and International Pharmaceutical Abstracts (January 1966-March 2010). Articles selected were limited to those published in the English language. Reference citations from relevant publications identified were also reviewed. Study Selection and Data Extraction: All English-language articles identified were reviewed and 17 trials (14 prospective and 3 retrospective) involving alternate-day statin dosing were included. Studies involving alternative statin dosing regimens other than alternating days were excluded from this review. Data Synthesis: Daily administration of statins is the standard of therapy used to reduce low-density lipoprotein cholesterol (LDL-C) levels as well as atherosclerosis that may lead to coronary events. Through LDL-C lowering and pleiotrope effects, statins decrease cardiovascular morbidity and mortality. Unfortunately, due to cost and adverse effects of statins, some patients are nonadherent to statin therapy. Several small studies have found alternate-day statin therapy to be as effective at reducing LDL-C as daily administration, while also lowering the incidence of adverse reactions and potentially lowering cost. Conclusions: Alternate-day statin therapy may decrease cost and therapy-limiting adverse reactions while potentially increasing regimen adherence and positively affecting the lipid panel. Further research is needed to determine whether this alternative regimen produces similar cardiovascular outcomes as those with daily statin therapy,

Vancomycin Combined With Clindamycin for the Treatment of Acute Bacterial Skin and Skin-Structure Infections

BACKGROUND Acute bacterial skin and skin-structure infections (ABSSSIs) are common causes of hospital admissions. These infections are often caused by methicillin-resistant Staphylococcus aureus; therefore, vancomycin remains a commonly used therapy. The purpose of this study was to compare hospital length of stay (LOS) in patients treated with vancomycin monotherapy vs combination therapy with clindamycin for ABSSSIs. METHODS This was a retrospective analysis of 269 patients admitted with ABSSSIs to a 941-bed hospital in northern Alabama. Patients who received either vancomycin monotherapy or vancomycin in combination with clindamycin were included. The primary outcome was hospital LOS; secondary outcomes included 90-day readmission rate and the impact of the following on the primary outcome: organisms cultured, presence of abscess, incision and debridement (I&D), failure of a trial of outpatient antibiotics, and presence of diabetes. RESULTS Hospital LOS was similar between groups when evaluating all ABSSSIs (3.7 ± 1.5 days vs 4.0 ± 2.0 days, P = .192, combination and monotherapy, respectively). In patients with abscesses, combination therapy was significantly associated with decreased LOS by 18.2% compared with monotherapy (95% confidence interval [CI], 0.818 [.679 to .985]; P = .034). Among the entire population, significantly fewer patients in the combination group were readmitted within 90 days (5.3% vs 15.3%; P = .006; odds ratio [OR], 3.2; 95% CI [1.35 to 7.66]). The 90-day readmission rates were significantly lower among patients with abscesses as well (2.0% vs 24.3%; P = .0001; OR, 14.6; 95% CI [2.98 to 71.37]). CONCLUSIONS Combination therapy with vancomycin and clindamycin was associated with decreased hospital LOS for patients with an abscess. The 90-day hospital readmission rates for those with ABSSSIs may be reduced when combination therapy is utilized. A larger, prospective, multicentered study is needed to validate these findings.

ABCs of ABGs : A Guide to Interpreting Acid-Base Disorders

Purpose This objective of this article is to provide a useful resource on the assessment of arterial blood gasses (ABGs) for clinical pharmacists, pharmacy residents, and students. Summary Acid-base pathophysiology can be separated into metabolic or respiratory acidosis and alkalosis, as well as those disturbances that are compensated. This article provides readers with a stepwise approach for assessing ABGs, as well as offering actual case examples to familiarize the reader with the concepts of acid-base disorders. By the completion, the reader will have the tools necessary to assess any ABG that may be encountered in clinical practice. Conclusion Comprehension of acid-base pathophysiology is a complicated and overwhelming task for novice and experienced clinicians alike. Utilization of the stepwise approach proposed in this article will help clinicians at all levels of training assess and develop treatment options for any acid-base disturbance encountered in practice.

Development of an antibiogram in a long-term care facility.

OBJECTIVE To create an antibiogram-a profile of an organisms susceptibility/resistance to a panel of antibiotics- for a long-term care facility to assess the prevalence of resistance of bacteria present at the facility. DESIGN Retrospective analysis of culture and sensitivity data from July 1, 2009, through June 30, 2010. SETTING A long-term care facility in Huntsville, Alabama. PATIENTS AND PARTICIPANTS Residents of the long-term care facility that had one or more culture and sensitivity test performed. MAIN OUTCOME MEASURE Susceptibility of bacteria to each antimicrobial tested. RESULTS Results were compiled and reported according to the Clinical and Laboratory Standards Institute Analysis and Presentation of Cumulative Antimicrobial Susceptibility Test Data. The most commonly seen bacteria in our long-term care facility were Escherichia coli, Staphylococcus aureus, Enterococcus faecalis, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis. Resistance rates for these bacteria were high and included the presence of methicillinresistant S. aureus and extended-spectrum beta-lactamase-producing bacteria. CONCLUSION Resistance rates were high among all organisms reported. This poses a serious threat to the health care teams ability to effectively treat residents of this facility. Development of an antibiogram to assist physicians in antimicrobial selection will be beneficial in helping evaluate trends in drug resistance to current available treatments. Implementing clinical pathways for empiric treatment of infections could improve the ability to provide consistent treatment for all residents in the facility.

An Update on the Management of Nosocomial Pneumonia

Nosocomial pneumonia is the second most common hospital-acquired infection, after urinary tract infection; however, it carries with it a mortality rate estimated to be between 20% and 50%. Furthermore, patients with nosocomial pneumonia are hospitalized for an additional 7 to 9 days with an attributable cost of

Neuroleptic Malignant Syndrome: No Longer Exclusively a “Neuroleptic” Phenomenon

40 000 or more per patient compared to patients without nosocomial pneumonia. While treatment options vary, initial empiric treatment of nosocomial pneumonia should include antimicrobials that will have activity against the organisms that will likely be encountered, including, but not limited to, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter species, Klebsiella pneumoniae, Enterobacter subspecies, Serratia marcescens, and Stenotrophomonas maltophilia. During a time of increasing resistance, it is crucial that early recognition along with appropriate treatment and dosing strategies are employed to achieve successful outcomes. The goal of this article is to update clinicians about nosocomial pneumonia and provide information regarding caveats to selecting and dosing antimicrobials, so informed decisions can be made when treating this serious condition.